Acrylamide exposure increases cardiovascular risk of general adult population probably by inducing oxidative stress, inflammation, and TGF-ß1: A prospective cohort study.

Acrylamide (ACR) exposure and consequent health hazards are alarming public health issues that attract worldwide concern. The World Health Organization urges more researches into health hazards from ACR exposure. However, whether and how ACR exposure increases cardiovascular risk remain unclear, and we sought to address these issues in this prospective cohort study conducted on 3024 general adults with 3-year follow-up (N = 871 at follow-up). Individual urinary ACR metabolites (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) as credible biomarkers of ACR exposure were detected to assess their cross-sectional and longitudinal relationships with 10-year cardiovascular disease (CVD) risk, a well measure of overall cardiovascular risk. Besides, biomarkers of oxidative stress (urinary 8-hydroxy-deoxyguanosine [8-OHdG] and 8-iso-prostaglandin-F2α [8-iso-PGF2α]) and inflammation (circulating mean platelet volume [MPV] and plasma C-reactive protein [CRP]) as well as plasma transforming growth factor-ß1 (TGF-ß1) were measured to assess their mediating/mechanistic roles in the relationships of ACR metabolites with 10-year CVD risk. We found AAMA, GAMA, and ΣUAAM (AAMA + GAMA) were cross-sectionally and longitudinally related to increased 10-year CVD risk with odds ratios (95% confidence intervals [CIs]) of 1.32 (1.04, 1.70), 1.81 (1.36, 2.40), and 1.40 (1.07, 1.82), respectively, and risk ratios (95% CIs) of 1.99 (1.10, 3.60), 2.48 (1.27, 4.86), and 2.13 (1.15, 3.94), respectively. Furthermore, 8-OHdG, 8-iso-PGF2α, MPV, CRP, and TGF-ß1 were found to significantly mediate 8.06-48.92% of the ACR metabolites-associated 10-year CVD risk increment. In summary, daily ACR exposure of general adults was cross-sectionally and longitudinally associated with increased cardiovascular risk, which was partly mediated by oxidative stress, inflammation, and TGF-ß1, suggesting for the first time that ACR exposure may well increase cardiovascular risk of general adult population partly by mechanisms of inducing oxidative stress, inflammation, and TGF-ß1. Our findings have important public health implications that provide potent epidemiological evidence and vital mechanistic insight into cardiovascular risk increment from ACR exposure.

The preventive effect of taxifolin on acrylamide-induced heart damage in rats / O efeito preventivo da taxifolina em danos cardíacos induzidos por acrilamida em ratos

ABSTRACT Objective Acrylamide is a toxic compound widely used in industrial sectors. Acrylamide causes reactive oxygen species formation and the subsequent lipid peroxidation reaction, which plays an important role in the pathogenesis of oxidative damage. Taxifolin is a flavonoid with antioxidant properties that inhibit reactive oxygen species formation. In this study, we aimed to investigate the preventive effect of taxifolin on acrylamide-induced oxidative heart damage. Methods The rats were divided into three groups: Acrylamide, Acrylamide+Taxifolin , and Healthy group. Water and food intake and body weight alterations were recorded daily. Malondialdehyde, total glutathione, nuclear factor kappa-B, total oxidant status, and total antioxidant status levels were analyzed from the heart tissue. Troponin-I levels, the parameter known as a cardiac biomarker, were analyzed from the blood sample. The cardiac histopathologic examination was also performed. Results In the Acrylamide group animals, the malondialdehyde, nuclear factor kappa-B, total oxidant status, and troponin-I levels were significantly higher compared to the ones of Acrylamide+Taxifolin and Healthy groups. The levels of total glutathione and total antioxidant status were significantly lower compared to Acrylamide+Taxifolin and Healthy groups'. Additionally, in the Acrylamide group, body weight gain, food and water intake, significantly declined compared to the Acrylamide+Taxifolin and Healthy groups. However, in the Acrylamide+Taxifolin group, taxifolin supplementation brought these values close to Healthy group ones. Furthermore, taxifolin treatment ameliorated structural myocardial damage signs induced by acrylamide. Conclusion Acrylamide exposure significantly induced oxidative damage to rat heart tissue. Taxifolin was able to improve the toxic consequences of acrylamide biochemically and histopathologically, possibly due to its antioxidant properties.

RESUMO Objetivo A acrilamida é um composto tóxico amplamente utilizado em setores industriais. Ela causa a formação de reativas de oxigênio e subsequente reação de peroxidação lipídica, que desempenham um papel importante na patogênese do dano oxidativo. A taxifolina é um flavonóide com propriedades antioxidantes que inibe a formação de reativas de oxigênio. Neste estudo, o objetivo foi investigar o efeito preventivo da taxifolina no dano cardíaco oxidativo induzido por acrilamida. Métodos Os ratos foram divididos em três grupos: Acrilamida, Acrilamida+Taxifolina e grupo Saudável. Ingestão de água e comida e alterações de peso corporal dos animais foram registradas diariamente. Malondialdeído, glutationa total, fator nuclear kappa-B, estado oxidante total e estado antioxidante total foram analisados no tecido cardíaco dos ratos. Os níveis de troponina-I, - parâmetro conhecido como biomarcador cardíaco, foram analisados a partir de amostra de sangue. Um exame histopatológico cardíaco também foi realizado. Resultados Nos animais do grupo Acrilamida, os níveis de malondialdeído, fator nuclear kappa-B, estado oxidante total e troponina-I foram significativamente maiores em comparação com os do grupo Acrilamida+Taxifolina e Saudável. Os níveis de glutationa total e estado antioxidante total foram significativamente mais baixos em comparação com grupos Acrilamida+Taxifolina e Saudável. Além disso, no grupo Acrilamida, o ganho de peso corporal e a ingestão de alimentos e água diminuíram significativamente em comparação com os animais dos grupos Acrilamida+Taxifolina e Saudável. No entanto, no grupo Acrilamida+Taxifolina, a suplementação com taxifolina aproximou esses valores aos do grupo Saudável. Além disso, o tratamento com taxifolina melhorou os sinais de dano miocárdico estrutural induzidos pela acrilamida. Conclusão A exposição à acrilamida induziu significativamente o dano oxidativo do tecido cardíaco dos ratos. A taxifolina foi capaz de melhorar as consequências tóxicas da acrilamida bioquímica e histopatologicamente, possivelmente devido às suas propriedades antioxidantes.

The Effect of Anakinra on Acrylamide-induced Peripheral Neuropathy and Neuropathic Pain in Rats

Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1ß, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties

Dietary Acrylamide Intake and the Risk of Hematological Malignancies: The Japan Public Health Center-Based Prospective Study.

Acrylamide, which is present in many daily foods, is a probable human carcinogen. In 2002, it was identified in several common foods. Subsequently, western epidemiologists began to explore the relationship between dietary acrylamide exposure and cancer risk; however, limited suggestive associations were found. This prospective study aimed to examine the association between dietary acrylamide intake and the risk of hematological malignancies, including malignant lymphoma (ML), multiple myeloma (MM), and leukemia. We enrolled 85,303 participants in the Japan Public Health Center-based Prospective study on diet and cancer as from 1995. A food frequency questionnaire that included data on acrylamide in all Japanese foods was used to assess dietary acrylamide intake. We applied multivariable adjusted Cox proportional hazards models to reckon hazard ratios (HRs) for acrylamide intake for both categorical variables (tertiles) and continuous variables. After 16.0 median years of follow-up, 326 confirmed cases of ML, 126 cases of MM, and 224 cases of leukemia were available for final multivariable-adjusted analysis. HRs were 0.87 (95% confidence interval [CI]: 0.64-1.18) for ML, 0.64 (95% CI: 0.38-1.05) for MM, and 1.01 (95% CI: 0.71-1.45) for leukemia. Our results implied that acrylamide may not be related to the risk of hematological malignancies.

Acrylamide Induces Mitophagy and Alters Macrophage Phenotype via Reactive Oxygen Species Generation.

Acrylamide is a readily exposed toxic organic compound due to its formation in many carbohydrate rich foods that are cooked at high temperatures. Excessive production of reactive oxygen species (ROS), which is an important factor for mitophagy, has been reported to lead to airway inflammation, hyper-responsiveness, and remodeling. Epigenetic regulation is an important modification affecting gene transcription. In this study, the effects of acrylamide on ROS productions and mitophagy were investigated. The human monocytic cell line THP-1 was treated with acrylamide, and ROS productions were investigated by flow cytometry. The mitochondrial and epigenetic involvement was evaluated by quantitative real-time PCR. Histone modifications were examined by chromatin immunoprecipitation assays. Mitophagy was detected by Western blotting and confocal laser microscopy. Acrylamide promoted mitochondria-specific ROS generation in macrophages. The gene expression of mitochondrial respiratory chain complex II SDHA was increased under acrylamide treatment. Acrylamide induced histone H3K4 and H3K36 tri-methylation in an SDHA promoter and increased mitophagy-related PINK1 expression, which promoted a M2-like phenotypic switch with increase TGF-ß and CCL2 levels in THP-1 cells. In conclusion, acrylamide induced ROS production through histone tri-methylation in an SDHA promoter and further increased the expression of mitophagy-related PINK-1, which was associated with a macrophage M2 polarization shift.

Dietary Acrylamide Intake and the Risk of Pancreatic Cancer: The Japan Public Health Center-Based Prospective Study.

Acrylamide is a probable carcinogen in humans. Few studies have assessed dietary acrylamide intake and the risk of pancreatic cancer; however, these studies are based on Western populations. Our purpose was to investigate the association of dietary acrylamide intake with the risk of pancreatic cancer utilizing data from the Japan Public Health Center-based Prospective Study. We evaluated the data of 89,729 participants aged 45-74 years, who replied to a questionnaire on past medical history and lifestyle habits from 1995-1998. Dietary acrylamide intake was estimated utilizing a validated food frequency questionnaire. We calculated the hazard ratios and 95% confidence intervals by using Cox proportional-hazards regression models. The average follow-up was 15.2 years, and 576 cases of pancreatic cancer were diagnosed. In the multivariate-adjusted model, an association between dietary acrylamide intake and pancreatic cancer risk was not demonstrated (hazard ratio for the highest vs. lowest quartile = 0.83, 95% confidence interval: 0.65-1.05, p for trend = 0.07). Furthermore, in the analyses stratified by sex, smoking status, coffee consumption, green tea consumption, alcohol consumption, and body mass index, no significant association was detected. Dietary acrylamide intake was not associated with the pancreatic cancer risk in Japanese individuals.

The Coffee-Acrylamide Apparent Paradox: An Example of Why the Health Impact of a Specific Compound in a Complex Mixture Should Not Be Evaluated in Isolation.

The health implications of acrylamide in food are a matter of concern based on toxicological studies in rodents, which showed that doses of acrylamide more than 100 times higher than those estimated to result from dietary exposure in humans are carcinogenic; however, the cancer types reported in rodents are species-specific, and whether these results can be extrapolated to humans is still in question. In fact, human epidemiological studies revealed a general lack of association between dietary acrylamide exposure and the incidence of different cancer types. Even occupational exposure to acrylamide, resulting in acrylamide exposure nearly 10 times higher than dietary exposure, did not increase tumor occurrence. Furthermore, the consumption of coffee, which is a main contributor of dietary acrylamide exposure, actually decreases the overall incidence of cancer in humans and afford global health benefits, increasing both lifespan and healthspan on ageing. This paradox clearly illustrates the risk of evaluating an individual molecule independently of its complete food matrix, which may have other components that completely override the effects of the considered molecule.

Dietary Acrylamide Intake and Risk of Lung Cancer: The Japan Public Health Center Based Prospective Study.

Acrylamide, which forms in heat-treated foods with high carbohydrate content, is a probable human carcinogen. This study aimed to evaluate the association between dietary acrylamide intake and lung cancer using data from the Japan Public Health Center based Prospective Study. Our study included 85,303 participants who completed a food frequency questionnaire. Cox proportional hazards regression models were used to assess hazard ratios and 95% confidence intervals (CIs) after adjusting for confounders. After 14.3 years and 15.4 years of mean follow-up period, 1187 and 485 lung cancer cases were identified in men and women, respectively. The multivariable-adjusted hazard ratios of 10-µg/day increment in acrylamide intake were 1.01 (95% CI, 0.99-1.02) in men and 0.98 (95% CI, 0.95-1.02) in women. Compared with the lowest quartile of acrylamide intake, the hazard ratios for the highest quartile were 1.13 (95% CI, 0.95-1.33; p for trend = 0.12) in men and 1.03 (95% CI, 0.78-1.36; p for trend = 0.86) in women in the multivariable-adjusted model. Moreover, there was also no significant association observed in the stratified analysis for histological subtypes of lung cancer. This study demonstrated that dietary acrylamide intake was not associated with increased lung cancer risk in the Japanese population.

Dietary Acrylamide Intake and the Risk of Liver Cancer: The Japan Public Health Center-Based Prospective Study.

Acrylamide has been studied for its carcinogenicity in experimental animals, causing tumors at several organ sites, and has been considered probably carcinogenic to humans as well. Given the small number of epidemiological studies that have been conducted, it is still uncertain whether the consumption of acrylamide is associated with liver cancer. Therefore, we investigated a study to determine the possible relationship between acrylamide intake and the risk of developing liver cancer in the Japanese population. A total of 85,305 participants, from the Japan Public Health Center-based Prospective Study, who provided a validated food-frequency questionnaire were enrolled between 1995 and 1998. During a median of 16.0 years follow-up, 744 new liver cancer cases were identified. Compared to the lowest tertile of acrylamide consumption (<4.8 µg/day), the multivariate hazard ratio (HR) for the highest tertile (≥7.6 µg/day) was 0.79 (95% confidence interval [CI] = 0.65-0.95) for liver cancer using multivariable model 1, adjusted for smoking status, body mass index (BMI), physical activity, medical history, and alcohol consumption; whereas the inverse relationship disappeared after additionally adjusting for coffee consumption in multivariable model 2 with HR of 1.08 (95% CI = 0.87-1.34) for the highest tertile. The effect of dietary acrylamide intake on the risk of liver cancer was not observed in the Japanese population.

In vivo assessment of the protection conferred by ß-glucans from Pleurotus ostreatus against the harmful effects of acrylamide intake (Part I).

INTRODUCTION: Introduction: acrylamide is formed in food through Maillard's reaction during thermal processing, and has been shown to be neurotoxic in humans, and a possible carcinogen. Studies have shown that ß-glucans from Pleurotus ostreatus have diverse biological properties such as antioxidant and anticancer activities. Objective: the aim of this work was to evaluate the protective effect of ß-glucans from Pleurotus ostreatus against the harmful effects of acrylamide consumption in mice. Methods: ß-glucans were obtained by alkaline-acid hydrolysis of Pleurotus ostreatus, and the content was characterized by liquid chromatography. To evaluate the effect of ß-glucans on the expression of glutathione, Balb/c mice were used, and 4 test groups were established. All groups were fed normally, and the groups treated with acrylamide were administered the compound intragastrically at a concentration of 50 g/mL; ß-glucans were administered at a concentration of 50 g/mL. Results: mice exposed to acrylamide showed a marked variation in the activity of glutathione enzymes in the liver. Significant differences (p < 0.05) were only found in the expression of glutathione transferase, which was increased almost 3 times in the group treated with ß-glucans as compared with the control group, and 1.5 times as compared with the group treated with acrylamide. Conclusions: the results show that ß-glucans could act by increasing the activity of enzymes involved in xenobiotic detoxification, thus protecting the biological system against the harmful effects caused by acrylamide intake.

INTRODUCCIÓN: Introducción: la acrilamida se forma en los alimentos a través de la reacción de Maillard durante el proceso térmico, y ha demostrado ser neurotóxica en humanos y un posible carcinógeno. Algunos estudios han demostrado que los ß-glucanos de Pleurotus ostreatus tienen diversas propiedades biológicas, como actividades antioxidantes y anticancerígenas. Objetivo: el objetivo de este trabajo fue evaluar el efecto protector de los ß-glucanos de Pleurotus ostreatus contra los efectos nocivos por consumo de acrilamida en ratones (prueba in vivo). Métodos: los ß-glucanos se obtuvieron por hidrólisis ácido-alcalina de Pleurotus ostreatus y su contenido se caracterizó por cromatografía líquida. La oxidación de los lípidos se evaluó mediante el método de TBARS, y para evaluar el efecto de los ß-glucanos en la expresión de glutatión se usaron ratones Balb/c, y se establecieron 4 grupos de prueba. Todos los grupos fueron alimentados normalmente; a lo grupos tratados con acrilamida, esta se les administró intragástricamente en una concentración de 50 µg/ml, y los ß-glucanos en una concentración de 50 µg/ml. Resultados: en el presente trabajo, los ratones expuestos a acrilamida mostraron una marcada variación en la actividad de las enzimas de glutatión determinadas en el hígado. Solo se encontraron diferencias significativas (p < 0,05) en la expresión de glutatión-transferasa, que aumentó casi 3 veces en el grupo tratado con ß-glucano en comparación con el grupo de control, y 1,5 veces con respecto al grupo tratado con acrilamida. Conclusiones: los resultados muestran que los ß-glucanos podrían actuar como agentes antioxidantes que protegen el hígado contra el estrés oxidativo causado por la ingesta de acrilamida.

Associations between nutritional factors and KRAS mutations in colorectal cancer: a systematic review.

BACKGROUND: Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. Here, we conducted a systematic review to summarize the current epidemiological evidence on the association between various dietary factors and KRAS mutations. METHODS: PubMed, Science Direct, and Cochrane databases were searched for relevant studies published until December 31, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find associations between nutritional factors and CRC tumors with KRAS mutations in humans. RESULTS: We identified 28 relevant studies to include in this systematic review. In-depth analyses showed unclear associations between nutritional factors and KRAS mutations in CRC. Most epidemiological studies in the same nutrient or food often reported conflicting and/or inconclusive findings, whereas for some dietary factors, the results were homogeneous. CONCLUSIONS: Further research using a more robust prospective cohort study is needed to lend more credence to the epidemiological associations found between KRAS mutations and dietary factors.

Protective effect of punicalagin, the main polyphenol compound of pomegranate, against acrylamide-induced neurotoxicity and hepatotoxicity in rats.

Acrylamide (ACR) is widely used in industries. Oxidative stress and apoptosis pathways are important mechanisms behind ACR-induced hepatotoxicity and neurotoxicity. Regarding to antioxidant and antiapoptotic properties of punicalagin (PUN), the protective effect of this agent on ACR-induced toxicity in rat was evaluated. Rats were divided into seven groups: control, ACR (50 mg/kg/day, i.p.), PUN (10, 20, and 40 mg/kg/day, i.p.) plus ACR, vitamin E (200 mg/kg, i.p.) plus ACR, and PUN groups. After 11 days, the gait score test was evaluated. Then, the animals were sacrificed and the malondialdehyde (MDA) and glutathione (GSH) contents were determined in the brain and liver tissues. Apoptosis-involved factors and myelin basic protein (MBP) were determined by western blotting. Severe movement disorder, MDA enhancement, and GSH reduction in the brain and liver tissues were observed in ACR-treated animals. The Bax/Bcl2 ratio and caspase-3 levels were enhanced in the tested tissues. ACR elevated the level of aspartate aminotransferases and decreased serum protein and albumin concentration. PUN recovered movement disorders, changed the level of markers which are important in oxidative stress and reduced apoptosis. Also, PUN increased the MBP level which was reduced due to ACR toxicity. PUN can protect against ACR-induced toxicity through antioxidant and antiapoptotic properties.

Dietary acrylamide exposure from traditional food products in Lesser Poland and associated risk assessment.

INTRODUCTION AND OBJECTIVE: Acrylamide (AA) is a carcinogenic and genotoxic food contaminant occurring in carbohydrate-rich foods produced at high cooking temperatures. The aim of the study was to determine the importance of AA exposure with respect to traditional food and to assess the associated risks. MATERIAL AND METHODS: 165 food samples were collected from local markets in Lesser Poland. The participants enrolled in the study were 500 residents: (males - 179, females - 321) who had purchased food from local markets. Exposure of the participants to AA was assessed by combining the analytical AA results with data on the individual consumption of traditional foods. Risk assessment of AA exposure from traditional foods was estimated and the margin of exposure (MOE) values were calculated. RESULTS: The highest mean AA level was measured in pretzels (92 µg kg -1), followed by bagels (74.81 µg kg-1) and pork paté (59.56 µg kg-1). The average and 95th percentile values of AA exposure were 0.213 and 0.458 [µg kg-1 body weight (BW) day-1]. The calculated values of MOE for the average [798 and 2,019 for both benchmark dose lower confidence limit (BMDL) 0.17 and 0.43 mg kg-1 BW day-1] and 95th percentile AA exposure values (371 and 939 for both BMDL 0.17and 0.43 mg kg -1 BW day-1) suggest that there is a health concern with respect to adult residents. CONCLUSIONS: The results of the study confirm the general recommendation to the consumers, especially certain population groups, to eat a balanced healthy diet and to limit the amount of baked cereal products and fried products.

Dietary Intake of Acrylamide and Risk of Breast, Endometrial, and Ovarian Cancers: A Systematic Review and Dose-Response Meta-analysis.

Acrylamide is a probable human carcinogen. Aside from occupational exposures and smoking, diet is the main source of exposure in humans. We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast, endometrial, and ovarian cancers in nonexperimental studies published through February 25, 2020, and conducted a dose-response meta-analysis. We identified 18 papers covering 10 different study populations: 16 cohort and two case-control studies. Acrylamide intake was associated with a slightly increased risk of ovarian cancer, particularly among never smokers. For endometrial cancer, risk was highest at intermediate levels of exposure, whereas the association was more linear and positive among never smokers. For breast cancer, we found evidence of a null or inverse relation between exposure and risk, particularly among never smokers and postmenopausal women. In a subgroup analysis limited to premenopausal women, breast cancer risk increased linearly with acrylamide intake starting at 20 µg/day of intake. High acrylamide intake was associated with increased risks of ovarian and endometrial cancers in a relatively linear manner, especially among never smokers. Conversely, little association was observed between acrylamide intake and breast cancer risk, with the exception of premenopausal women.

A urinary metabolomic study from subjects after long-term occupational exposure to low concentration acrylamide using UPLC-QTOF/MS.

Because long-term occupational exposure to low concentrations of acrylamide (ACR) has the potential to cause neurological damage, it is important to identify biomarkers that can be used to evaluate this risk. In the present study, urine metabolomics of the ACR-exposed and non-exposed groups to identify potential metabolites was carried out using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. Serum biochemical indexes of the exposed and non-exposed groups were also determined. Principal component analysis showed a differential separation between exposed group and non-exposed group and a total of 7 metabolites were identified in positive and negative ionization modes; Area under curve of anthranilic acid, ß-guanidinopropionic acid and mesobilirubinogen were 0.980, 0.843 and 0.801 respectively and these metabolites showed high sensitivity and specificity. The 13 biochemical indexes were divided into three classes based on physiological functions. Only biomarkers of dysregulated liver function including alanine aminotransferase, aspartic transaminase, total bilirubin, direct bilirubin and triglyceride were significantly higher in the exposed group than in the non-exposed group. This study identifies important related metabolic changes in the bodies of workers after long-term occupational exposure to low concentration ACR and suggests new biomarkers of nervous system injury caused by ACR. The study also provides a sound basis for exploring the biochemical mechanisms and metabolic pathways of nervous system toxicity caused by ACR.

Evaluation of the protective effects of Ganoderma atrum polysaccharide on acrylamide-induced injury in small intestine tissue of rats.

This research investigated the protective effects of Ganoderma atrum polysaccharide (PSG-1) on acrylamide (AA) induced intestinal injury in rats. Our results showed that PSG-1 pretreatment effectively reduced the levels of malondialdehyde (MDA), but increased the activity of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and the total glutathione (T-GSH), and significantly reduced oxidative stress in AA treated rats. Furthermore, PSG-1 pretreatment down-regulated pro-inflammatory cytokines i.e. interleukin 2 (IL-2), interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and increased the amounts of anti-inflammatory cytokines i.e. interleukin 4 (IL-4) and interleukin 10 (IL-10), significantly reducing an inflammatory response in the intestines of rats. In AA induced intestinal injury, the tissue uric acid (UA) level and alkaline phosphatase (ALP) activity and the serum level of d-lactic acid (d-lactate), nitric oxide (NO) and endothelin-1 (ET-1) decreased significantly after treatment with PSG-1 and N-acetylcysteine (NAC). Histological observations of the small intestine confirmed the protective effects of different doses of PSG-1. These findings suggested that PSG-1 pretreatment could alleviate AA-induced oxidative stress, reduce inflammatory response, and inhibit AA absorption by protecting the intestinal barrier. Therefore, Ganoderma atrum polysaccharide has the potential to be a dietary supplement ingredient that provides protection against AA-induced gut injury.

Dietary Acrylamide Intake and Risk of Esophageal, Gastric, and Colorectal Cancer: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Acrylamide has been classified as a probable human carcinogen based chiefly on laboratory evidence. However, the influence of dietary acrylamide intake on risk of esophageal, gastric, and colorectal cancer has not been extensively studied. We aimed to evaluate the association between dietary acrylamide intake and esophageal, gastric, and colorectal cancer using data from the Japan Public Health Center-based Prospective Study. METHODS: Our study included 87,628 participants who completed a food-frequency questionnaire at enrollment in 1990 and 1993. We used Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals (CI) after adjusting for confounding factors. RESULTS: After 15.5, 15.3, and 15.3 mean years of follow-up for esophageal, gastric, and colorectal cancer, we identified and analyzed 391 esophageal, 2,218 gastric, and 2,470 colorectal cancer cases, respectively. Compared with the lowest quintile of acrylamide intake, the multivariate HR for the highest quintile was 0.86 (95% CI, 0.53-1.39; P trend = 0.814), 0.84 (95% CI, 0.69-1.01; P trend = 0.301), and 0.93 (95% CI, 0.79-1.08; P trend = 0.165) for esophageal, gastric, and colorectal cancer, respectively, in the multivariable-adjusted model. Furthermore, no significant associations were observed when the participants were stratified by cancer subsites. CONCLUSIONS: In conclusion, this study demonstrated that dietary acrylamide intake was not associated with increased risk of esophageal, gastric, or colorectal cancer among the Japanese population. IMPACT: It is the first time to assess the effect of dietary acrylamide intake on risk of digestive system cancer in Asian populations.

Health risk assessment of acrylamide in bread in Iran using LC-MS/MS.

Acrylamide is a chemical, often present in bread, legally classified as carcinogen, mutagen and reproductive toxicant. Since bread is consumed both world-wide and in Iran, determination of acrylamide in different types of breads is of high interest. In the present study, acrylamide was monitored in 56 Sangak and 30 industrial bread samples collected from Tehran and Shiraz, using LC-MS/MS (LOQ = 1 ng/g). In addition, the noncarcinogenic risk (target hazard quotient-THQ) and carcinogenic risk (incremental lifetime cancer risk-ILCR) due to ingestion of acrylamide through bread consumption in children and adults were assessed. Acrylamide was detected in more than 90% of the samples tested. The average daily intake of acrylamide in Iran based on exclusive consumption of Sangak bread, was estimated at 145 ng/kg bw/day. Based on the THQ for bread acrylamide in adults and children, the decreasing risk order was: Shiraz semi-industrial Sangak, Shiraz traditional Sangak, Tehran traditional Sangak, Tehran industrial bread. The ILCR of bread acrylamide calculated for adults and children was higher than the permissible lifetime carcinogenic risk value established by USEPA (1.00E-5). Results show that bread is a major source of acrylamide intake by people in Iran and all consumers regardless of age could be at elevated carcinogenic risk.

Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk.

PURPOSE: The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology. METHODS: The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n = 1449) and ER+ breast cancer cases (n = 844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3 years of follow-up. RESULTS: Unexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+ breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+ breast cancer risk. CONCLUSIONS: This study did not provide evidence for a positive association between acrylamide intake and ER+ breast cancer risk. If anything, acrylamide was associated with a decreased ER+ breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+ breast cancer risk through sex hormone pathways.

Dietary Acrylamide Is Not Associated with Renal Cell Cancer Risk in the CPS-II Nutrition Cohort.

BACKGROUND: Acrylamide, an industrial chemical and probable human carcinogen, can be formed in primarily carbohydrate-containing foods during high-heat cooking or processing. Most epidemiologic studies show no associations of dietary acrylamide intake with most cancer outcomes, but limited prospective evidence suggests a positive association with renal cell carcinoma (RCC). METHODS: In 1999, 102,154 men and women from the Cancer Prevention Study-II Nutrition Cohort completed a questionnaire on diet, lifestyle, and cancer risk factors and were followed through June 30, 2013. Cox proportional hazards regression was used to estimate the HR and 95% confidence interval (CI) for the association between estimated dietary acrylamide intake and risk of RCC. RESULTS: After 1,137,441 person-years of follow-up, 412 cases of invasive RCC occurred. In multivariable-adjusted models, there was no association between acrylamide intake and risk of RCC (HR = 1.09; 95% CI, 0.82-1.43) for the highest versus lowest quartile of intake. Associations were not modified by sex or smoking history. CONCLUSIONS: We found no associations between dietary acrylamide exposure and risk of invasive RCC. IMPACT: The findings from this large, prospective analysis do not support a positive association between higher dietary acrylamide intake and RCC risk.